Abnormalities of CD4+ T cell subpopulations in ANCA-associated vasculitis
Abnormalities of CD4+ T cell subpopulations in ANCA-associated vasculitis
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DOI：
10.1111/j.1365-2249.2005.02731.x
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发表时间：
2005-04-01
影响因子：
4.6
通讯作者：
Van Der Woude, FJ
中科院分区：
文献类型：
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作者：
Marinaki, S;Neumann, I;Van Der Woude, FJ
在ANCA相关性血管炎（AAV）患者中，循环T细胞上的CD 25表达增加。虽然在动物实验中，CD 4（+）CD 25（+）T调节细胞（T-reg）在抗自身免疫保护中的作用已得到充分证实，但这些细胞在AAV中的作用尚不清楚。为了研究T细胞上CD 25表达增加与持续的T细胞活化有关，而与腺相关病毒中T-reg细胞的干扰无关的假设（34名患者，其中6名是肾移植后），我们研究了不同亚群中的CD 25表达CD 4（+）细胞和FOXP 3 mRNA表达通过逆转录聚合酶链反应（RT-PCR）。此外，T细胞增殖和细胞因子分泌后的刺激与抗-CD 3和抗-CD 28和细胞内细胞因子的生产后的刺激与佛波醇肉豆蔻酸酯乙酸酯（PMA）-离子霉素进行了测定。对照组为非血管炎肾移植患者（n = 9）和健康对照（HC）（n = 13）。在AAV中，淋巴细胞总数、CD 4（+）淋巴细胞和幼稚T细胞的百分比低于HC和RTX。在AAV和AAV/RTX中发现CD 25（+）细胞百分比增加，与疾病活动无关，但在HC或RTX中没有。这仅限于初始（CD 4（+）CD 45 RB（高））人群。在AAV患者和健康对照组中，CD 4（+）T细胞中FOXP 3 mRNA的表达没有差异。与HC相比，AAV患者的T细胞体外增殖能力增强（P < 0.01）。抗CD 3/CD 28刺激后，AAV患者PBMC产生的白细胞介素（IL）-10和IFN-γ显著减少。与HC相比，患者中IL-10和IL-12的百分比显著更高，但IFN-γ、IL-4或肿瘤坏死因子（TNF）-α产生细胞的百分比不显著更高。这些发现仅限于CD 4（+）细胞的记忆群体。我们的结论是，AAV患者淋巴细胞减少，CD 4（+）T细胞数量低，这似乎是在一个持续的激活状态。
In patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4(+) CD25(+) T-regulatory-cells (T-reg) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in T-reg cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4(+) cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). In addition, T cell proliferation and cytokine secretion after stimulation with anti-CD3 and anti-CD28 and intracellular cytokine production after stimulation with phorbol myristate acetate (PMA)-ionomycin was determined. Controls were non-vasculitic renal transplant patients (n = 9) and healthy controls (HC) (n = 13). In AAV the total number of lymphocytes, CD4(+) lymphocytes and the percentage of naive T cells are lower than in HC and RTX. An increased percentage of CD25(+) cells was found in AAV and AAV/RTX, irrespective of disease activity, but not in HC or RTX. This was confined to the naive (CD4(+) CD45RB(high)) population only. FOXP3 mRNA expression in CD4(+) T cells did not differ between AAV patients and healthy controls. In vitro T cell proliferation was enhanced in AAV patients compared to HC (P < 0.01). PBMC of AAV patients produced significantly less interleukin (IL)-10 and interferon (IFN)-gamma after anti-CD3/CD28 stimulation. The percentage of IL-10 and IL-12, but not IFN-gamma, IL-4 or tumour necrosis factor (TNF)-alpha-producing cells was significantly higher in patients compared to HC. These findings were confined to the memory population of CD4(+) cells. We conclude that AAV patients are lymphopenic and have low numbers of CD4(+) T cells, which seem to be in a persistent state of activation.